Substituted 1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acids

Abstract

Indole derivatives characterized by having a 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid nucleus bearing a substituent in position 1 and 4. The nucleus may be optionally substituted at position 8. The derivatives are useful anti-inflammatory and analgesic agents and methods and chemical intermediates for their preparation are also disclosed. Included are compounds of the formula ##STR1## wherein R 1 is --H or lower alkyl containing 1 to 3 carbon atoms; R 2 is --NH 2 , --NHCHO, --NHCONH 2 , --OCH 3 , oxo; R 3 is --H or lower alkyl containing 1 to 3 carbon atoms and the pharmaceutically acceptable salts thereof when R 1 is --H.

We claim: 
     
       1. The compounds having the structure (I) ##STR5## wherein R 1  is --H or lower alkyl containing 1 to 3 carbon atoms; R 2  is --NH 2 , ,--NHCHO, --NHCONH 2 , --OCH 3 , oxo; R 3  is --H or lower alkyl containing 1 to 3 carbon atoms and the pharmaceutically acceptable salts thereof when R 7  is --H. 
     
     
       2. The compounds according to claim 1 wherein R 1  is --H or methyl; R 2  is --NH 2 , --NHCHO, --NHCONH 2 , --CH 3  or oxo; and R 3  is --H or ethyl and the pharmaceutically acceptable salts thereof when R 7  is --H. 
     
     
       3. The compounds according to claim 1 wherein R 1  is methyl; R 2  is --NH 2 , or --NHCHO; and R 3  is --H or ethyl. 
     
     
       4. The compounds according to claim 2 wherein R 1  is --H; R 2  is --NHCONH 2  or oxo; R 3  is --H or ethyl and the pharmaceutically acceptable salts thereof. 
     
     
       5. The compound according to claim 3 designated 4-amino-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl ester. 
     
     
       6. The compound according to claim 2 designated 1,8-diethyl-4-methoxy-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl ester. 
     
     
       7. The compound according to claim 2 designated 4-[(aminocarbonyl)amino]-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl ester. 
     
     
       8. The compound according to claim 2 designated 1,8-diethyl-1,3,4,9-tetrahydro-4-oxopyrano[3,4-b]indole-1-acetic acid methyl ester. 
     
     
       9. The compound according to claim 2 designated 1-ethyl-4-amino-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl ester. 
     
     
       10. The compound according to claim 4 designated 4-[(aminocarbonyl)amino]-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid and the pharmaceutically acceptable salts thereof. 
     
     
       11. The compound according to claim 4 designated 1,8-diethyl-1,3,4,9-tetrahydro-4-oxopyrano[3,4-b]indole-1-acetic acid and the pharmaceutically acceptable salts thereof. 
     
     
       12. A pharmaceutical composition for treating inflammatory or painful conditions in a mammal comprising an effective amount of a compound of structure (I), or a pharmaceutically acceptable salt thereof, as defined in claim 4 and a pharmaceutically acceptable carrier. 
     
     
       13. A pharmaceutical composition for treating inflammatory or painful conditions in a mammal comprising an effective amount of a compound of structure (I), or a pharmaceutically acceptable salt thereof, as defined in claim 4, a nonsteroid anti-inflammatory drug selected from the group consisting of ibuprofen and aspirin, an opiate analgesic selected from the group consisting of codeine, oxycodone and morphine and a pharmaceutically acceptable carrier. 
     
     
       14. A method for treating inflammatory or painful conditions in a mammal which comprises the administration to said mammal of an effective amount of a compound selected from those of formula (I), or a pharmaceutically acceptable salt thereof, as defined in claim 4. 
     
     
       15. A method for treating inflammatory or painful conditions in a mammal which comprises the administration to said mammal of an effective amount of a compound selected from those of formula (I), or a pharmaceutically acceptable salt thereof, as defined in claim 4, in conjunction with nonsteroid anti-inflammatory drugs selected from the group consisting of ibuprofen and aspirin and opiate analgesics selected from the group consisting of codeine, oxycodone and morphine.